Cited by 371Fungal and yeast genetics researchGene Regulatory Network AnalysisBacterial Genetics and Biotechnology

Bet Hedging in Yeast by Heterogeneous, Age-Correlated Expression of a Stress Protectant

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Levy, Sasha F., Ziv, Naomi, Siegal, Mark L.·2012·PLoS Biology

Abstract

Genetically identical cells grown in the same culture display striking cell-to-cell heterogeneity in gene expression and other traits. A crucial challenge is to understand how much of this heterogeneity reflects the noise tolerance of a robust system and how much serves a biological function. In bacteria, stochastic gene expression results in cell-to-cell heterogeneity that might serve as a bet-hedging mechanism, allowing a few cells to survive through an antimicrobial treatment while others perish. Despite its clinical importance, the molecular mechanisms underlying bet hedging remain unclear. Here, we investigate the mechanisms of bet hedging in Saccharomyces cerevisiae using a new high-throughput microscopy assay that monitors variable protein expression, morphology, growth rate, and survival outcomes of tens of thousands of yeast microcolonies simultaneously. We find that clonal populations display broad distributions of growth rates and that slow growth predicts resistance to heat killing in a probabalistic manner. We identify several gene products that are likely to play a role in bet hedging and confirm that Tsl1, a trehalose-synthesis regulator, is an important component of this resistance. Tsl1 abundance correlates with growth rate and replicative age and predicts survival. Our results suggest that yeast bet hedging results from multiple epigenetic growth states determined by a combination of stochastic and deterministic factors.

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Crossref · 10.1371/journal.pbio.1001325

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  • From the perspective of population evolution, heteroresistance can be seen as a strategy that helps the fungal population survive diverse environments.

    “From the perspective of population evolution, it can be seen as a strategy that helps the fungal population survive diverse environments [100].”

    From Insight into the Mechanisms and Clinical Relevance of Antifungal Heteroresistance (2025) · cites this paper as [100]

    The Discussion describes heterogeneous yeast states that confer different fitness across environments, supporting the population-level bet-hedging interpretation. But the paper studies variation in heat-stress survival, not heteroresistance, and Box 1 says whether this bet hedging is adaptive remains to be tested. It therefore does not establish that heteroresistance helps fungal populations survive diverse environments. (LLM, conf=0.85)

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Research works printed but not linked: 2

  1. [87]Seger J Brockmann H 1987 What is bet-hedging? Oxford surveys in evolutionary biology, vol. 4 Oxford Oxford University Press 182 211
  2. [90]Acar M Mettetal J. T van Oudenaarden A 2008 Stochastic switching as a survival strategy in fluctuating environments. Nat Genet 40 471 475 18362885

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Authors
Levy, S. F., Ziv, N., & Siegal, M. L.
Affiliations
New York University (US)
Corresponding author
  • Levy, Sasha F.
  • Siegal, Mark L.
Venue
PLoS Biology
Published
2012-05-08
Volume
10
Issue
5
Pages
e1001325
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W1967330678
Cited by
371
References
93
Citations by year
2026: 21 · 2025: 21 · 2024: 27 · 2023: 19 · 2022: 23 · 2021: 29 · 2020: 25 · 2019: 14 · 2018: 34 · 2017: 32 · 2016: 25 · 2015: 36 · 2014: 32 · 2013: 27 · 2012: 6
FWCI
12.99
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Science Foundation (0642999)
  • National Institutes of Health
  • National Institute of General Medical Sciences (F32GM079909, F32GM79909)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords
bet-hedging, cellular heterogeneity, stochastic gene expression, Saccharomyces cerevisiae, trehalose biosynthesis, growth rate variability, heat resistance, stress tolerance, microcolonies
MeSH terms
Flow Cytometry, Genes, Fungal, Hot Temperature, Microscopy, Mutation, Saccharomyces cerevisiae, Stochastic Processes, Time Factors, Colony Count, Microbial, Models, Statistical, Gene Expression Regulation, Fungal, Heat-Shock Response, Saccharomyces cerevisiae Proteins, Epigenesis, Genetic, Green Fluorescent Proteins, Genetic Fitness, Time-Lapse Imaging

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